Moderate hypoglycaemia obliterates working memory in humans with and without insulin treated diabetes

Deary, Ian J.; Sommerfield, A. J.; McAulay, Vincent; Frier, Brian M.

doi:10.1136/jnnp.74.2.278-a

Cited by 32 publications

(31 citation statements)

References 5 publications

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“…We have demonstrated previously that episodic short-, working-and longterm memory are significantly impaired by hypoglycaemia [2][3][4]. These results are in agreement with earlier reports, which included some tests of memory among broader cognitive test batteries, but much remains to be elucidated about the functioning of memory during hypoglycaemia.…”

Section: Introductionsupporting

confidence: 92%

Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non‐diabetic adults

Warren

Sommerfield

Greve

et al. 2007

Diabetes Metabolism Res

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One hour of hypoglycaemia at 2.5 mmol/L induced 20-40 min after learning did not disrupt memory consolidation. fMRI did not show evidence of altered brain activation after hypoglycaemia. Consolidation may be relatively resistant to hypoglycaemia, or may have been complete before hypoglycaemia was induced. The study was powered to detect a large effect, and provides some reassurance that moderate hypoglycaemia does not cause major disruption of previously learned memories in people with insulin-treated diabetes.

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Section: Introductionsupporting

confidence: 92%

Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non‐diabetic adults

Warren

Sommerfield

Greve

et al. 2007

Diabetes Metabolism Res

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Section: Hypoglycaemia and Hypoglycaemia Unawarenessmentioning

confidence: 99%

“…Diminished brain function during acute hypoglycaemia leads to potential physical danger and, moreover, recurrent hypoglycaemia imposes long-lasting damaging effects on brain function [150,151]. Cognitive performance is altered during experimentally induced hypoglycaemia [152][153][154][155][156][157][158], and some studies in patients with T1D suggested an association between recurrent hypoglycaemia and cognitive impairment [11,16,[159][160][161][162].During severe hypoglycaemia, the absence of sufficient glucose supply to the brain leads to neuroglycopenia that results in energy deprivation and thus other substrates are mobilised for ATP synthesis. Hypoglycaemia causes a reduction in brain glycogen and lactate levels and then depletes metabolic intermediates, namely glucose-6-phosphate, pyruvate, citrate, 2-oxoglutarate and malate [163], and leads to progressive reduction of brain glutamate, glutamine, GABA and alanine with concomitant increase in aspartate that can efficiently act on NMDA receptors [164][165][166][167][168].…”

mentioning

confidence: 99%

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

Duarte¹

2014

aging dis

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From epidemiological studies it is known that diabetes patients display increased risk of developing dementia. Moreover, cognitive impairment and Alzheimer's disease (AD) are also accompanied by impaired glucose homeostasis and insulin signalling. Although there is plenty of evidence for a connection between insulin-resistant diabetes and AD, definitive linking mechanisms remain elusive. Cerebrovascular complications of diabetes, alterations in glucose homeostasis and insulin signalling, as well as recurrent hypoglycaemia are the factors that most likely affect brain function and structure. While difficult to study in patients, the mechanisms by which diabetes leads to brain dysfunction have been investigated in experimental models that display phenotypes of the disease. The present article reviews the impact of diabetes and AD on brain structure and function, and discusses recent findings from translational studies in animal models that link insulin resistance to metabolic alterations that underlie brain dysfunction. Such modifications of brain metabolism are likely to occur at early stages of neurodegeneration and impact regional neurochemical profiles and constitute non-invasive biomarkers detectable by magnetic resonance spectroscopy (MRS).Key words: Neurodegeneration, Diabetes, Alzheimer's disease, Insulin, Metabolism Diabetes mellitus can be defined as a chronic metabolic disorder characterized by hyperglycaemia, resulting from inappropriate insulin secretion and/or action [1]. The vast majority of the diabetes cases are included in two main categories, classified according to the underlying cause, which are type 1 diabetes (T1D) or insulindependent diabetes, generally caused by an autoimmune reaction to antigens of pancreatic β-cells, leading to impaired insulin production, and type 2 diabetes (T2D) or insulin-resistant diabetes, characterised by inefficiency of insulin action. While T1D is mainly observed in children and adolescents, T2D is more common among adults, accounting for more than 90% of the diabetes cases worldwide. The prevalence of diabetes and impaired glucose tolerance achieved now epidemic proportions, respectively at 6.9% and 8.3% of the world population, and predicted to raise to 8. 0% and 10.1% in 2035 [2]. Moreover, diabetes is nowadays a leading cause of death accounting for 8.4% of global mortality in people aged between 20 and 79 years [2]. The main contributor for the high prevalence of diabetes is the rise of obesity, related to the combination of ample food availability and a sedentary lifestyle, contrasting to less abundant food supplies and higher physical activity observed until a century ago.Diabetes is associated with the occurrence of well described microvascular complications that affect different organs, leading most commonly to retinopathy, nephropathy and peripheral neuropathy, which development is dependent on the duration of the disease and glycaemia control [3]. When the control of the disorder allowed patients to live longer and without these Volume 6, N...

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“…Hypoglycaemia impairs the auditory and visual processing subsystems of sensory memory, short-term memory, working memory and delayed memory in both diabetic and nondiabetic subjects [11][12][13][14][15][16]. Working memory and delayed memory are particularly susceptible to hypoglycaemia [17].…”

Section: Introductionmentioning

confidence: 99%

The effects of acute hypoglycaemia on memory acquisition and recall and prospective memory in type 1 diabetes

et al. 2006

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Aims/hypothesis Global memory performance is impaired during acute hypoglycaemia. This study assessed whether moderate hypoglycaemia disrupts learning and recall in isolation, and utilised a novel test of prospective memory which may better reflect the role of memory in daily life than conventional tests. Subjects and methods Thirty-six subjects with type 1 diabetes participated, 20 with normal hypoglycaemia awareness (NHA) and 16 with impaired hypoglycaemia awareness (IHA). Each underwent a hypoglycaemic clamp with target blood glucose 2.5 mmol/l. Prior to hypoglycaemia, subjects attempted to memorise instructions for a prospective memory task, and recall was assessed during hypoglycaemia. Subjects then completed the learning and immediate recall stages of three conventional memory tasks (word recall, story recall, visual recall) during hypoglycaemia. Euglycaemia was restored and delayed memory for the conventional tasks was tested. The same procedures were completed in euglycaemic control studies (blood glucose 4.5 mmol/l). Results Hypoglycaemia impaired performance significantly on the prospective memory task (p=0.004). Hypoglycaemia also significantly impaired both immediate and delayed recall for the word and story recall tasks (p<0.01 in each case). There was no significant deterioration of performance on the visual memory task. The effect of hypoglycaemia did not differ significantly between subjects with NHA and IHA. Conclusions/interpretation Impaired performance on the prospective memory task during hypoglycaemia demonstrates that recall is disrupted by hypoglycaemia. Impaired performance on the conventional memory tasks demonstrates that learning is also disrupted by hypoglycaemia. Results of the prospective memory task support the relevance of these findings to the everyday lives of people with diabetes.

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Moderate hypoglycaemia obliterates working memory in humans with and without insulin treated diabetes

Cited by 32 publications

References 5 publications

Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non‐diabetic adults

Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non‐diabetic adults

Metabolic Alterations Associated to Brain Dysfunction in Diabetes

The effects of acute hypoglycaemia on memory acquisition and recall and prospective memory in type 1 diabetes

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